The development of collagen-GAG scaffold-membrane composites for tendon tissue engineering

Current tissue engineering approaches for tendon defects require improved biomaterials to balance microstructural and mechanical design criteria. Collagen-glycosaminoglycan (CG) scaffolds have shown considerable success as in vivo regenerative templates and in vitro constructs to study cell behavior. While these scaffolds possess many advantageous qualities, their mechanical properties are typically orders of magnitude lower than orthopedic tissues such as tendon. Taking inspiration from mechanically efficient core-shell composites in nature such as plant stems and porcupine quills, we have created core-shell CG composites that display high bioactivity and improved mechanical integrity. These composites feature integration of a low density, anisotropic CG scaffold core with a high density, CG membrane shell. CG membranes were fabricated via an evaporative process that allowed separate tuning of membrane thickness and elastic moduli and were found to be isotropic in-plane. The membranes were then integrated with an anisotropic CG scaffold core via freeze-drying and subsequent crosslinking. Increasing the relative thickness of the CG membrane shell was shown to increase composite tensile elastic modulus by as much as a factor of 36 in a manner consistent with predictions from layered composites theory. CG scaffold-membrane composites were found to support tendon cell viability, proliferation, and metabolic activity in vitro, suggesting they maintain sufficient permeability while demonstrating improved mechanical strength. This work suggests an effective, biomimetic approach for balancing strength and bioactivity requirements of porous scaffolds for tissue engineering.